Abstract
Alzheimer's disease (AD) involves progressive accumulation of amyloid β-peptide (Aβ) and neurofibrillary pathologies, and glucose hypometabolism in brain regions critical for memory. The 3xTgAD mouse model was used to test the hypothesis that a ketone ester-based diet can ameliorate AD pathogenesis. Beginning at a presymptomatic age, 2 groups of male 3xTgAD mice were fed a diet containing a physiological enantiomeric precursor of ketone bodies (KET) or an isocaloric carbohydrate diet. The results of behavioral tests performed at 4 and 7 months after diet initiation revealed that KET-fed mice exhibited significantly less anxiety in 2 different tests. 3xTgAD mice on the KET diet also exhibited significant, albeit relatively subtle, improvements in performance on learning and memory tests. Immunohistochemical analyses revealed that KET-fed mice exhibited decreased Aβ deposition in the subiculum, CA1 and CA3 regions of the hippocampus, and the amygdala. KET-fed mice exhibited reduced levels of hyperphosphorylated tau deposition in the same regions of the hippocampus, amygdala, and cortex. Thus, a novel ketone ester can ameliorate proteopathic and behavioral deficits in a mouse AD model.
Original language | English (US) |
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Pages (from-to) | 1530-1539 |
Number of pages | 10 |
Journal | Neurobiology of Aging |
Volume | 34 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2013 |
Externally published | Yes |
Keywords
- 3xTgAD
- Amygdala
- Anxiety
- Cognitive deficits
- Energy Metabolism
- Frontotemporal lobe dementia
- Hippocampus
ASJC Scopus subject areas
- Clinical Neurology
- General Neuroscience
- Aging
- Developmental Biology
- Geriatrics and Gerontology